Drug-coated stents can improve the overall effectiveness of angioplasty and stenotic procedures performed on the cardiovascular system and other vessels within the body by delivering potent therapeutic compounds at the point of infarction. Drugs such as anti-inflammatants and anti-thrombogenics may be dispersed within the drug-polymer coating and released in a controlled manner after the insertion and deployment of a stent. These drugs and coatings can reduce the trauma to the local tissue bed, aid in the healing process, and significantly reduce the narrowing or constriction of the blood vessel that can reoccur where the stent is placed.
Stenting procedures have had a major impact on the field of interventional cardiology and endovascular surgery. Much medical research and development in the last decade have been dedicated to stents, and in the most recent years, to drug-eluting coatings for stents. The efficacy of vascular stents is potentially increased by the addition of stent coatings that contain pharmaceutical drugs. These drugs may be released from the coating while in the body, delivering their patent effects at the site where they are most needed. Thus, the localized levels of the medications can be elevated, and therefore potentially more effective than orally- or intravenously-delivered drugs that distribute throughout the body, the latter which may have little effect on the impacted area, or which may be expelled rapidly from the body without achieving their pharmaceutical intent. Furthermore, drugs released from tailored stent coatings may have controlled, timed-release qualities, eluting their bioactive agents over hours, weeks or even months.
In practice, a common solvent or pair of solvents is used to dissolve the drug and polymer. The polymer may include copolymers or polymer blends. Then the drug-polymer solution is sprayed on the stents. Upon drying, the drug-polymer is formed on the stent surface. In this process, the drug-polymer ratio and polymer content for each formulation are fixed.
When the drug-coated stent is deployed in a vessel in the body, the drug release is predominantly based on a diffusion mechanism. Drug diffusion is controlled in part by the molecular size, the crystallinity, and the hydrophilic-lipophilic balance of the drug, as well as the morphology of the polymeric coating, the glass temperature Tg of the polymer and the polymer crystallinity. For most drugs, there is a common releasing profile: a burst release occurs where a large amount of drug gets released initially, followed by a slow, gradual release that leads to a gradually decaying effect where drug elution from the stent diminishes with time. This typical releasing profile occurs because of the resistance offered by the polymer film to the transport of drug to the surface, and the reduction of the drug supply from within the coating.
Several classes of drug-polymer chemistries have been explored for use in stent coatings, as found in the current art. A composition with a bioactive agent for coating the surface of a medical device based on poly (alkyl)(meth)acrylate and poly(ethyline-co-vinyl acetate) is described in “Bioactive Agent Release Coating,” Chudzik et al., U.S. Pat. No. 6,214,901, issued Apr. 10, 2001. A composite polymer coating with a bioactive agent and a barrier coating formed in situ by a low-energy plasma polymerization of a monomer gas is described in U.S. Pat. No. 6,335,029, “Polymeric Coatings for Controlled Delivery of Active Agents,” K. R. Kamath et al., issued Jan. 1, 2002. Another polymeric coating for an implantable medical article is presented in “Implantable Medical Device,” E. Koulik et al., U.S. Pat. No. 6,270,788, issued Aug. 7, 2001. This stent coating is based on hydrophobic methacrylate and acrylate monomers, a functional monomer having pendant chemically reactive amino groups capable of forming covalent bonds with biologically active compounds, and a hydrophilic monomer, wherein a biomolecule is coupled to the coated surface. Use of block copolymers on a hydrophobic polymer substrate is described in “Biocompatible Polymer Articles,” E. Ruckenstein et al., U.S. Pat. No. 4,929,510, issued May 29, 1990.
In selecting polymers for drug delivery, three important criteria must be met: polymer biocompatibility, satisfactory mechanical properties such as durability and integrity during roll down and expansion of the stent, and correct release profiles for the drugs. Candidate chemistries for drug polymers may result in an excessively rapid elution of an incorporated drug. When a drug is eluted too quickly, it may be ineffective. When a drug is eluted too slowly, the pharmaceutical intent may remain unfulfilled. Furthermore, if insufficient drug is delivered after stent deployment, the potential benefits of time-released drugs may be compromised by inadequate dosages.
Unfortunately, some drug polymers do not provide the mechanical flexibility necessary to be effectively used on a stent. A stent may be deployed by self-expansion or balloon expansion, accompanied by a high level of bending at portions of the stent framework, which can cause cracking, flaking, peeling, or delaminating of many candidate drug polymers while the stent diameter is increased by threefold or more during expansion. The candidate drug polymer may not stick or adhere. Furthermore, the coating may fall off, crystallize or melt during preparation and sterilization prior to deployment, further limiting the types of drug polymers acceptable for use on cardiovascular stents.
It is desirable to have a medicated stent that can be tailored to provide a desired elution rate profile for one or more drugs, without compromising the mechanics of the stent during deployment and use. A preferred drug-polymer system can be tailored to accommodate a variety of drugs for controlled time delivery, while maintaining mechanical integrity during stent deployment. Of additional benefit is a polymeric system that can be readily altered to control the elution rate of interdispersed bioactive drugs and to control their bioavailability Furthermore, a more desirable polymer-drug system can be tailored to enhance or diminish the burst effect of drug delivery after stent deployment, and to enhance the ability to deliver drugs over extended periods of time.
It is an object of this invention, therefore, to provide a framework and structure for effective, controlled delivery of suitable quantities of pharmaceutical agents from medicated stents. Additional objects of this invention include providing a system and method for treating heart disease and other vascular conditions, providing methods of manufacturing drug-polymer coated stents, and overcoming the deficiencies and limitations described above.